Biofidelic skin simulant

ABSTRACT

Described are biofidelic skin simulants closely mimicking the biomechanical properties of natural human skin, including vaginal skin tissue. The simulant contains a crosslinked siloxane network.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Applications62/189,504, filed Jul. 7, 2015, and 62/263,942, filed Dec. 7, 2015, thecontents of which are hereby incorporated in their entirety.

BACKGROUND

The skin is the outer protective covering of the human body with anaverage total area close to 20 square feet, and composed of three layersnamely the epidermis (outermost soft layer), the dermis (middle layer),and hypodermis (inner most layer made of strong connective tissues),with an average thickness of 1-4 mm. The skin is the first point ofcontact for any external load with the human body, and also the firstbarrier against any physical injury.

Skin simulants have been developed for burnt skin replacements and formedical training, such as for phlebotomical and surgical practice. Skinsimulants are also useful in a variety of design and testingapplications. For instance, skin simulants are employed during thedevelopment of ballistic munitions, especially in the context ofnon-lethal projectiles.

A successful skin simulant should accurately mimic the biomechanicalproperties of natural skin. Skin is a viscoelastic material and exhibitsnon-linear strain behavior. Furthermore, skin is not homogenous acrosseither a single individual or a group of individuals. A single humanwill have skin tissues of differing stiffness, thickness and, dependingon the specific location the skin occurs on the human body. As skinages, collagen and other cellular components degrade, leading the skinto become less stiff.

Historically, intact skin obtained from human cadavers has been employedas a simulant, as well as skin samples from animals such as pigs, goats,and sheep. However, these materials present both ethical and practicalchallenges stemming from the harvesting and storage of biologicaltissues. As such, the use of synthetic skin simulants has been explored.U.S. Pat. No. 7,222,525 discloses skin/tissue simulant prepared from agelatin block overlaid with an ether-cast polyurethane sheet. WO2013/171444 describes a skin simulant prepared from a synthetic chamois,which can be prepared from various polymeric materials such as cotton,viscose, polyvinyl acetate, polyesters, and nylon-polyamide. Thesesimulants, however, do not truly mimic the non-linear hyperelasticproperties of true human skin.

Despite extensive research, a skin simulant having the realisticnon-linear hyperelastic properties of the human skin has not yet beenachieved. Realistic skin simulants would be of great use in a variety ofbiomechanical testing applications. For instance, a realistic simulantcould be used to estimate the load response of cosmetic implants, or tofurther study the mechanics of skin injuries. A realistic skin simulantwould be an invaluable aid for developing surgical techniques,especially for vaginal and other unique tissue types. In vaginalprolapse (POP), tissue stiffens progressively, making it difficult forsurgeons to correctly suture and implants corrective devices. Faultyvaginal mesh surgeries have caused substantial pain and suffering inmany women, and have resulted in malpractice lawsuits cumulativelytotaling over 100 million dollars annually. To date, training forurogynoecological surgeries is limited due to the limited availabilityof vaginal tissue. In addition to ethical and safety concerns associatedwith sampling human vaginal tissue, it is known that vaginal tissueobtained from a cadaver is not the same as living tissue. As such,efforts to develop improved urogynocological techniques have beenhampered.

The development of non-lethal and less-lethal munitions is an activearea of research in the ballistics industry. A simulant with realisticmechanical properties of the human skin is essential in order toaccurately predict the lethality of such munitions prior to theirdeployment in the field. The compositions and methods disclosed hereinaddress these and other needs.

SUMMARY

In accordance with the purposes of the disclosed methods, as embodiedand broadly described herein, the disclosed subject matter relates tocompositions and methods of making and using the compositions. Morespecifically, according to the aspects illustrated herein, there areprovided biofidelic skin simulants and methods of making and using thebiofidelic skin simulants disclosed herein.

According to further aspects illustrated herein, biofidelic skinsimulants are provided. The disclosed biofidelic skin simulants cancomprise one or more crosslinked siloxane polymers, wherein theparticular siloxane and degree of crosslinking are selected to produce asilicone network exhibiting the non-linear deformation properties ofnatural skin. Particularly disclosed herein are biofidelic skinsimulants closely mimicking normal and prolapsed vaginal skin tissue ata lower test rate. These simulants can be used to develop surgicaltechniques, including but not limited to those for prolapse surgery,hysterectomy, and surgeries associated with childbirth, such as cesareansection or episiotomy. Also disclosed herein are methods of makingbiofidelic skin simulants. The disclosed methods can comprise, forexample, crosslinking (or curing) one or more siloxane polymers in amanner sufficient to produce a silicone network exhibiting thenon-linear viscoelastic properties of natural skin.

Additional advantages will be set forth in part in the description thatfollows or may be learned by practice of the aspects described below.The advantages described below will be realized and attained by means ofthe elements and combinations particularly pointed out in the appendedclaims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying figures, which are incorporated in and constitute apart of this specification, illustrate several aspects described below.

FIG. 1, Panels A and B display stretch-stress plots for various skinsimulants in comparison to stretch-stress plots for naturally occurringhuman skin. The stretch ratio is plotted on the x-axis and the stress(MPa) is plotted on the y-axis.

FIG. 2 displays a stretch-stress plot for a skin simulant compared withnatural human skin. The stretch ratio is plotted on the x-axis and thestress (MPa) is plotted on the y-axis.

FIG. 3 displays stretch-stress (high stress range) plots for a skinsimulant compared with fresh pig skin. The stretch ratio is plotted onthe x-axis and the stress (MPa) is plotted on the y-axis.

FIG. 4 displays stretch-stress (low stress range) plots for a skinsimulant compared with fresh pig skin. The stretch ratio is plotted onthe x-axis and the stress (MPa) is plotted on the y-axis.

FIG. 5 displays stretch-stress plots of normal and prolapsed vaginaltissue collated from the scientific literature. The stretch ratio isplotted on the x-axis and the stress (MPa) is plotted on the y-axis.

FIG. 6 displays stretch-stress plots of various vaginal tissuesimulants. The stretch ratio is plotted on the x-axis and the stress(MPa) is plotted on the y-axis.

FIG. 7 displays stretch-stress plots of vaginal tissue simulants incomparison with literature derived vaginal tissue reports. The stretchratio is plotted on the x-axis and the stress (MPa) is plotted on they-axis. NPOP refers to non-prolapsed normal vaginal tissue, and POPrefers to prolapsed vaginal tissue.

FIG. 8 displays stretch-stress plots of repeated tests of a controlvaginal tissue simulant in comparison with mean normal vaginal tissueproperty derived from literature. The stretch ratio is plotted on thex-axis and the stress (MPa) is plotted on the y-axis.

FIG. 9 displays stretch-stress plots of repeated tests of a controlvaginal tissue simulant in comparison with non-prolapsed (normal)vaginal tissue property derived from literature. The stretch ratio isplotted on the x-axis and the stress (MPa) is plotted on the y-axis.NPOP refers to non-prolapsed normal vaginal tissue.

FIG. 10 displays stretch-stress plots of repeated tests of a controlvaginal tissue simulant in comparison with prolapsed vaginal tissueproperty derived from literature. The stretch ratio is plotted on thex-axis and the stress (MPa) is plotted on the y-axis. POP refers toprolapsed vaginal tissue.

DETAILED DESCRIPTION

The methods and compositions described herein may be understood morereadily by reference to the following detailed description of specificaspects of the disclosed subject matter and the Examples includedtherein.

Before the present methods and compositions are disclosed and described,it is to be understood that the aspects described below are not limitedto specific synthetic methods or specific reagents, as such may, ofcourse, vary. It is also to be understood that the terminology usedherein is for the purpose of describing particular aspects only and isnot intended to be limiting.

Also, throughout this specification, various publications arereferenced. The disclosures of these publications in their entiretiesare hereby incorporated by reference into this application in order tomore fully describe the state of the art to which the disclosed matterpertains. The references disclosed are also individually andspecifically incorporated by reference herein for the material containedin them that is discussed in the sentence in which the reference isrelied upon.

Definitions

In this specification and in the claims that follow, reference will bemade to a number of terms, which shall be defined to have the followingmeanings:

Throughout the description and claims of this specification the word“comprise” and other forms of the word, such as “comprising” and“comprises,” means including but not limited to, and is not intended toexclude, for example, other additives, components, integers, or steps.

As used in the description and the appended claims, the singular forms“a,” “an,” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a composition”includes mixtures of two or more such compositions, reference to “thecompound” includes mixtures of two or more such compounds, reference to“an agent” includes mixture of two or more such agents, and the like.

“Optional” or “optionally” means that the subsequently described eventor circumstance can or cannot occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not.

It is understood that throughout this specification the identifiers“first” and “second” are used solely to aid the reader in distinguishingthe various components, features, or steps of the disclosed subjectmatter. The identifiers “first” and “second” are not intended to implyany particular order, amount, preference, or importance to thecomponents or steps modified by these terms.

By substantially the same is meant the values are within 5% of oneanother, e.g., within 3%, 2% or 1% of one another.

As used herein, the term “silicone rubber” refers to three-dimensionalnetworks of cross-linked siloxane polymers. Unless specified otherwise,silicone rubbers include materials that are composed solely ofcrosslinked siloxane polymers, and materials that include other chemicalcompounds incorporated into the network. Such other chemical compoundscan be covalently incorporated into the network, or can be incorporatedinto the network through non-covalent interactions (e.g., hydrogenbonds, electrostatic bonds, Van der Waal bonds and the like).

As used herein, the term “non-linear hyperelastic” describes a materialin which some specified influence (such as stress) produces a response(such as strain or stretch) which is not proportional to the influence,and which can be characterized using constitutive curve fit equationsknown as the hyperelastic equations.

As used herein, the term “elasticity modulus (E) (low stretch ratio)”refers to the initial elasticity modulus or slope of the stress-stretchplot of a non-linear material approximated at low stretch values. Theway to measure this is to draw a line starting at the origin and tangentto the stress-stretch plot, and numerically estimate its slope.

As used herein, the term “elasticity modulus (E) (high stretch ratio)”refers to the final elasticity modulus or slope of the stress-stretchplot of a non-linear material before rupture. The way to measure this isto draw a line starting at the point of rupture and tangent to thestress-stretch plot, and numerically estimate its slope.

As used herein, the term “ultimate tensile strength” refers to the valueof stress applied to a material which just causes its rupture.

As used herein, the term “one-part siloxane” refers to a liquid siloxanecomposition which will undergo crosslinking in the absence of any addedchemical reagent. Exemplary one-part siloxanes include those cured byheat, light, moisture, and combinations thereof.

Some one-part siloxanes can undergo crosslinking when exposed to ambientconditions (˜23° C., standard humidity), whereas others requireadditional energy inputs (such as light or elevated heat) in order tocrosslink.

As used herein, the term “two-part siloxane (Part A),” or simply“siloxane (Part A),” refers to a liquid siloxane composition thatcontains a latent reactive silicone functional group that requiresactivation by the exposure to an additional chemical reagent.

As used herein, the term “two-part siloxane (Part B),” or simply“siloxane (Part B),” refers to a liquid siloxane composition thatcontains a chemical reagent that will activate a silicone functionalgroup to crosslinking.

Crosslinked siloxane networks can be characterized according to theShore (Durometer) hardness scale, as defined by the American Society forTesting and Materials (ATSM) D2240 testing standard. Shore (Durometer)hardness can be measured along several different scales, including “OO”,“A,” and “D”. Skin simulants can have, but are not limited to, networkshaving a Shore (Durometer) hardness from OO-10 to OO-60.

As used herein, the term “siloxane OO-10” refers to a liquid siloxanecomposition, which, when cured with another siloxane OO-10, will producea silicone network having a Shore (Durometer) hardness of OO-10. One ofordinary skill will appreciate that when a siloxane (Part A) OO-30 iscombined with an equal amount of siloxane (Part B) OO-30, the resultingnetwork will have a Shore (Durometer) hardness of OO-30. However, whentwo siloxanes of differing Shore (Durometer) hardness levels arecombined, the resulting network will have a Shore hardness differentthan either of the precursor siloxane components.

Biofidelic Skin Simulant

The biofidelic skin simulants disclosed herein have biomechanicalproperties similar to those of natural human skin. The biomechanicalproperties of human skin have been reported by Anniadh et al., in“Characterization of the anisotropic mechanical properties of excisedhuman skin,” JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS(2012) 5:139-148, which is incorporated by reference herein in itsentirety for its teaching of the mechanical properties of skin andmethods of measuring those properties. Anniadh describes the non-linearhyperelastic properties of human skin. In some embodiments, the skinsimulants disclosed herein exhibit non-linear properties falling withthe ranges provided by Anniadh for human skin.

In some embodiments, the skin simulant can be characterized by anelasticity modulus (E) (low stretch ratio) of at least 2, 2.5, 3, 3.5,4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8 MPa, where any of the stated valuescan form an upper or lower endpoint of a range. In some embodiments, theskin simulant can be characterized by an elasticity modulus (E) (lowstretch ratio) of no more than 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5,3, 2.5, or 2 MPa, where any of the stated values can form an upper orlower endpoint of a range. For instance, the elasticity modulus (E) (lowstretch ratio) can be from 2-8, 2-7.5, 2-7, 2-6.5, 2-6, 2-5.5, 2-5,2-4.5, 2-4, 2-3.5, 2-3, 2-2.5, 7.5-8, 7-8, 6.5-8, 6-8, 5.5-8, 5-8,4.5-8, 4-8, 3.5-8, 3-8, or 2.5-8 MPa. In some embodiments, theelasticity modulus (E) (low stretch ratio) can be from 4-8, 4-7.5, 4-7,4-6.5, 4-6, 4-5.5, 4-5, 4-4.5, 7.5-8, 7-8, 6.5-8, 6-8, 5.5-8, 5-8, or4.5-8 MPa.

The skin simulant can be characterized by an elasticity modulus (E)(high stretch ratio) of at least 6, 13, 20, 27, 34, 41, 48, 55, 62, 69,76, 83, or 90 MPa, where any of the stated values can form an upper orlower endpoint of a range. The skin simulant can be characterized by anelasticity modulus (E) (high stretch ratio) of no more than 90, 83, 76,69, 62, 55, 48, 41, 34, 27, 20, 13 or 6 MPa, where any of the statedvalues can form an upper or lower endpoint of a range. For instance, theelasticity modulus (E) (high stretch ratio) can be from 6-90, 6-83,6-76, 6-69, 6-62, 6-55, 6-48, 6-41, 6-34, 6-27, 6-20, 6-13, 83-90,76-90, 69-90, 62-90, 55-90, 48-90, 41-90, 34-90, 27-90, 20-90, or 13-90MPa. In some embodiments, the elasticity modulus (E) (high stretchratio) can be from 34-90, 34-83, 34-76, 34-69, 34-62, 34-55, 34-48,34-41, 83-90, 76-90, 69-90, 62-90, 55-90, 48-90, or 41-90 MPa.

In some embodiments, the skin simulant can be a vaginal skin simulant ata lower test rate. Prolapsed vaginal skin simulants can be characterizedby an elasticity modulus (E) (low stretch ratio) from 2-8, 2-7, 2-6,2-5, 2-4, 2-3, 6-7, 5-7, 4-7, or 3-7 MPa. Prolapsed vaginal skinsimulants can be characterized by an elasticity modulus (E) (highstretch ratio) from 12-60, 12-24, 12-36, 12-48, 48-60, 36-60, or 24-60MPa.

Normal vaginal skin simulants can be characterized by an elasticitymodulus (E) (low stretch ratio) from 0.3-2.7, 0.3-2.4, 0.3-2.1, 0.3-1.8,0.3-1.5, 0.3-1.2, 0.3-0.9, 0.3-0.6, 2.4-2.7, 2.1-2.7, 1.8-2.7, 1.5-2.7,1.2-2.7, 0.9-2.7, or 0.6-2.7 MPa. Normal vaginal skin simulants can becharacterized by an elasticity modulus (E) (high stretch ratio) from3-12, 3-9, 3-6, 9-12, or 6-12 MPa.

The skin simulant can be characterized by an ultimate tensile strengthof at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 MPa, where anyof the stated values can form an upper or lower endpoint of a range. Theskin simulant can be characterized by an ultimate tensile strength nogreater than 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 MPa, where anyof the stated values can form an upper or lower endpoint of a range. Theultimate tensile strength can be from 1-25, 1-20, 1-15, 1-10, 1-9, 1-8,1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 20-25, 15-25, 10-25, 9-25, 8-25, 7-25,6-25, 5-25, 4-25, 3-25, or 2-25 MPa. In some embodiments, the ultimatetensile strength can be from 5-20, 5-15, 5-10, 10-15, 15-20, 15-25, or20-25 MPa.

Hyperelastic constitutive equations are able to precisely curve fit thenon-linear stress versus stretch behavior of soft tissues such as thehuman skin. Veronda-Westmann hyperelastic stress and stretchrelationship for curve fitting an isotropic uniaxial mechanical testdata is given by equation (1), and the following table gives the curvefit parameters for all the 23 skin simulant samples tested. Samples 16,17, 18, 20, 21 and 22 are shown in FIG. 1, Panel B.

$\begin{matrix}{\sigma_{{Veronda} - {Westmann}} = {2( {\lambda^{2} - \frac{1}{\lambda}} )c_{1}{c_{2}( {^{c_{2}{({I_{1} - 3})}} - \frac{1}{2\lambda}} )}}} & (1)\end{matrix}$

Veronda-Westmann Hyperelastic model coefficients Sample c₁ c₂ 1 1.1 0.232 1 0.2 3 5.9 0.28 4 3.4 0.25 5 2.3 0.27 6 4 0.26 7 6 0.32 8 5.8 0.3 96.5 0.29 10 5.4 0.27 11 5.2 0.26 12 1.5 0.25 13 2 0.3 14 5 0.25 15 11.80.2 16 16 0.22 17 35 0.33 18 18 0.23 19 11.5 0.21 20 13.7 0.21 21 28 0.322 24 0.28 23 13.1 0.21

The skin simulants disclosed herein can be crosslinked siloxanenetworks. Suitable siloxane polymers for incorporation into the networkinclude those giving rise to silicone rubbers having a Shore (Durometer)hardness from 00-0 to 00-60, including 00-0, 00-10, 00-20, 00-30, 00-40,00-50, and 00-60. However, other siloxanes, for instance those which,when cured alone, result in more rigid elastomers, can also beincorporated into the skin simulant.

The skin simulants disclosed herein comprise silicone rubber. Siliconerubber is an elastomeric network of crosslinked siloxane polymers. Somesilicone rubbers are characterized as “one-part,” whereas others arereferred to as “two-part.” One and two-part silicone rubbers aredistinguished based on how they are cured. One part silicone rubbers areobtained by curing a single liquid siloxane precursor. Crosslinking suchone-part systems can occur in the presence of air, light, and/or heat.Two-part silicone rubbers are prepared by combining two separatesiloxane liquids. Each part contains a reactive component which, whencombined, initiates the crosslinking reacting. Two-part silicone systemsinclude addition-cured rubbers such as platinum cure rubbers,condensation-cured rubbers such as tin-cured rubbers, and peroxide-curedrubbers. The individual components of a two-part silicone rubber areoften designated “Part A” and “Part B.”

In certain embodiments, the skin simulants disclosed herein are madefrom a single one-part or two-part siloxane. Such simulants aredesignated herein as “unitary silicone simulants.” In other embodiments,the skin simulant is made from two different one-part or two-partsiloxanes. Such simulants are designated herein as “binary siliconesimulants.” Higher order systems, such as ternary or quaternary refer tosystems made from three, or four, different siloxanes (one-part ortwo-part), respectively.

In some embodiments, the skin simulant is a blend of at least onesiloxane having a Shore hardness from 00-0 to 00-15, and a secondsiloxane having a Shore hardness from 00-25 to 00-60. In someembodiments, the first siloxane has a Shore hardness from 00-05 to 00-15and the second siloxane has a Shore hardness from 00-25 to 00-40. Incertain examples, the first siloxane has a Shore hardness of 00-10 andthe second siloxane has a Shore hardness of 00-30.

For certain types of skin simulants, the first and second siloxane canbe present in a ratio from 1:99 to 20:80 by weight of the total siliconerubber. When either the first or second is a two part silicone system,the ratio includes the sum of both Parts A and B. The first siloxane,having a Shore hardness from 00-05 to 00-15, can be present in an amountthat is no more than 20%, 15%, 12%, 10%, 8%, 6%, 4%, or 2% by weight ofthe total siloxane content. The second siloxane, having a Shore hardnessfrom 00-25 to 00-40, can be present in an amount that is at least 80%,85%, 88%, 90%, 92%, 94%, 96%, or 98% by weight of the total siloxanerubber content.

In other examples, skin simulants having a different spectrum ofproperties can be obtained by blending a first siloxane, having a Shorehardness from 00-05 to 00-15, in an amount that is at least 50%, 55%,60%, 65%, 70%, 75%, or 80% by weight of the total siloxane content. Thesecond siloxane, having a Shore hardness from 00-25 to 00-40, can bepresent in an amount no more than 50, 45, 40, 35, 30, 25, or 20% byweight of the total siloxane content.

In some examples, the skin simulants, including those mimicking thevaginal skin simulants at a lower strain rate, can be obtained byblending a first siloxane having a Shore hardness of 00-10 and a secondsiloxane having a Shore hardness of 00-30. The first and secondsiloxanes can be mixed together in a weight ratio from 25:75 to 35:65,or 27.5:72:5 to 32.5:67.5, or 29:71 to 31:69. In certain selectedembodiments, the first and second siloxanes can be mixed together in aweight ratio from 35:65 to 40:60, or 35:65 to 37.5:62.5, or 37.5:62.5 to40:60, or 32.5:67.5 to 35:65.

Other components can be incorporated into the skin simulants. Forinstance, oils can be added to modify the overall stiffness of thesimulant, and dyes can be included to produce simulants of differingcolors.

Skin simulants can be prepared by combining one or more liquidsiloxanes, as well as any additional ingredients, in a mold and allowingthem to cure. Generally, all the siloxanes should be well blended toensure a uniform simulant. In other embodiments, however, a layeredsimulant can be prepared by sequentially curing different siloxanemixtures in a mold.

The skin simulants disclosed herein can be employed in a wide variety oftesting applications. For instance, real life injury scenarios can berecreated using a human skin surrogate and personal protective equipment(PPE) and safety systems in a wide range of applications, includingmilitary, automotive, biomedical, security, sports equipment etc. Theskin simulant can be used for extensive testing on the load response ofthe implants on the skin as well as for developing lighter and morereliable implant technologies in the future. The skin simulant materialcan also be used to design human torsos for estimating the dynamic loadresponse of ballistics for development of non-lethal and less-lethalballistic munitions in the future. Additionally, in the field ofergonomics, this human skin simulant can help estimate the discomfortlevel in individuals at different working conditions (such as a hardseat at work, loose car steering or a tight fitting dress of a swimmer).

The examples below are intended to further illustrate certain aspects ofthe methods and compounds described herein, and are not intended tolimit the scope of the claims.

EXAMPLES

The following examples are set forth below to illustrate the methods andresults according to the disclosed subject matter. These examples arenot intended to be inclusive of all aspects of the subject matterdisclosed herein, but rather to illustrate representative methods,compositions, and results. These examples are not intended to excludeequivalents and variations of the present invention, which are apparentto one skilled in the art.

Efforts have been made to ensure accuracy with respect to numbers (e.g.,amounts, temperature, etc.) but some errors and deviations should beaccounted for. Unless indicated otherwise, parts are parts by weight,temperature is in ° C. or is at ambient temperature, and pressure is ator near atmospheric. There are numerous variations and combinations ofreaction conditions, e.g., component concentrations, temperatures,pressures, and other reaction ranges and conditions that can be used tooptimize the product purity and yield obtained from the describedprocess. Only reasonable and routine experimentation will be required tooptimize such process conditions.

Example 1 Preparation of Biofidelic Skin Simulants

Binary skin simulants were prepared by blending together ECOFLEX 0010™and MOLDSTAR 30™. ECOFLEX 0010™ is a two-part platinum cure siliconerubber having a Shore (Durometer) hardness of 00-10. MOLDSTAR 30™ is atwo-part platinum cure silicone rubber having a Shore (Durometer)hardness of 00-30. Both products are commercially sold by Smooth-On,Inc. All four components were blended together, placed in a mold blank,and cured for an average of 6.5 hours at room temperature. By varyingthe size of the mold, skin simulant coupons were prepared having alength of 5 cm, a width of 1 cm, and thickness of either 1, 2, 3, or 4mm.

The following skin simulants were prepared:

ECOFLEX 0010 ™ MOLDSTAR 30 ™ Sample Part A Part B Part A Part B 1 45 455 5 2 45 45 5 5 3 15 15 35 35 4 42 42 8 8 5 42 42 8 8 6 35 35 15 15 712.5 12.5 37.5 37.5 8 12.5 12.5 37.5 37.5 9 10 10 40 40 10 15 15 35 3511 15 15 35 35 12 45 45 5 5 13 42 42 8 8 14 25 25 25 25 15 5 5 45 45 163 3 47 47 17 3 3 57 37 18 3 3 47 47 19 5 5 45 45 20 5 5 47 43 21 3 3 5440 22 3 3 52 42 23 4 4 46 46

The samples above were evaluated according to their stress-stretchresponse. The results are depicted in FIGS. 1A and 1B.

Sample 15 was tested to determine the reproducibility of itsstretch-stress response in comparison with human skin. The results aredepicted in FIG. 2.

Sample 15 was tested against freshly cut pig skin in both a high stress(FIG. 3) and low stress (FIG. 4) range.

Example 2 Vaginal Tissue Surrogates

The following skin simulants were prepared:

ECOFLEX 0010 ™ MOLDSTAR 30 ™ Sample Part A Part B Part A Part B  1 V15.66 14.25 34.42 35.77  2 V 15.25 13.92 34.08 36.75  3 V 14.08 13.9536.15 35.82  4 V 14.97 14.96 34.97 35.10  5 V 15.07 15.06 34.97 34.93  6V 8 8 42 42  7 V 30 30 20 20  8 V 15 15 35 35  9 V 48 32 10 10 10 V 2525 25 25 11 V 2 2 47 47 12 V 2 2 47 47 13 V 10 10 40 40 14 V 10 10 40 4015 V 15 15 35 35 16 V 42 42 8 8 17 V 42 42 8 8 18 V 45 45 5 5 19 V 45 455 5 20 V 50 50 0 0

The low and high stretch elasticity modulus (MPa/(mm/mm)) was determinedfor each of the above samples:

Low Stretch High Stretch Sample Elasticity Modulus Elasticity Modulus  1V 3.382 12.613  2 V 3.420 17.906  3 V 1.951 12.746  4 V 3.061 16.520  SV 3.164 14.162  6 V 5.078 19.503  7 V 1.329 9.097  8 V 2.122 11.935  9 V1.134 8.157 10 V 1.344 7.408 11 V 6.223 46.441 12 V 7.917 58.889 13 V4.660 20.620 14 V 5.297 29.186 15 V 3.232 12.613 16 V 0.871 10.353 17 V0.704 7.852 18 V 0.667 6.596 19 V 2.584 4.541 20 V 0.347 3.869

FIG. 6 depict the non-linear behavior of the above samples. FIGS. 7-10depict selected examples in comparison with normal and prolapsed tissuedata.

The Veronda-Westmann hyperelastic stress and stretch relationship wasdetermined. The following table lists the curve fit parameters for the20 vaginal simulant samples.

Sample C₁ (MPa) C₂ (MPa)  1 V 9.83 0.115  2 V 7.1 0.173  3 V 4.3 0.187 4 V 5.7 0.19  5 V 5.4 0.187  6 V 11.6 0.142  7 V 3.3 0.175  8 V 4.10.189  9 V 2.5 0.198 10 V 2.2 0.215 11 V 8.4 0.275 12 V 9.3 0.3 13 V11.8 0.14 14 V 8.5 0.215 15 V 9.9 0.116 16 V 1.3 0.32 17 V 0.9 0.34 18 V0.8 0.335 19 V 10 0.068 20 V 0.55 0.3

The methods and compositions of the appended claims are not limited inscope by the specific methods and compositions described herein, whichare intended as illustrations of a few aspects of the claims and anymethods and compositions that are functionally equivalent are within thescope of this disclosure. Various modifications of the methods andcompositions in addition to those shown and described herein areintended to fall within the scope of the appended claims. Further, whileonly certain representative methods, compositions, and aspects of thesemethods and compositions are specifically described, other methods andcompositions and combinations of various features of the methods andcompositions are intended to fall within the scope of the appendedclaims, even if not specifically recited. Thus a combination of steps,elements, components, or constituents can be explicitly mentionedherein; however, all other combinations of steps, elements, components,and constituents are included, even though not explicitly stated.

What is claimed is:
 1. A biofidelic skin simulant comprising acrosslinked siloxane network, wherein the skin simulant has a tensilestrength from 1 to 30 MPa; and an elasticity modulus (E) (low stretchratio) from 2 to 8 or an elasticity modulus (E) (high stretch ratio)from 42 to 90 MPa.
 2. The skin simulant according to claim 1, whereinthe network comprises a first siloxane having a Shore Hardness of from00-0 to 00-60, and a second siloxane having a Shore Hardness of from00-0 to 00-60, wherein the first and second siloxanes are different. 3.The skin simulant according to claim 1, wherein the first siloxane has aShore Hardness of 00-0, 00-10, or a mixture thereof.
 4. The skinsimulant according to claim 1, wherein the second siloxane has a ShoreHardness of 00-30, 00-40, 00-50, or a mixture thereof.
 5. The skinsimulant according to claim 1, wherein the first siloxane is present inan amount of 2-20% by weight relative to the total weight of thecrosslinked siloxane network.
 6. The skin simulant according to claim 1,wherein the first siloxane is present in an amount of 80-98% by weightrelative to the total weight of the crosslinked siloxane network.
 7. Theskin simulant according to claim 2, wherein the network comprises afirst siloxane having a Shore Hardness of 00-10 which is present in anamount from 25-35% by weight, and a second siloxane having a ShoreHardness of 00-30 which is present in an amount from 65-75% by weight.8. The skin simulant according to claim 1, which is a vaginal skinsimulants having a first siloxane having a Shore Hardness of 00-10 whichis present in an amount from 70-100% by weight, and a second siloxanehaving a Shore Hardness of 00-30 which is present in an amount from0-30% by weight.
 9. A method for preparing a biofidelic skin simulant,comprising curing a combination of a first siloxane having a ShoreHardness of from 00-0 to 00-60 and a second siloxane having a ShoreHardness of from 00-0 to 00-60 in a mold, wherein the first and secondsiloxanes are different.
 10. The method according to claim 9, whereinthe first siloxane has a Shore Hardness of 00-0, 00-10, or a mixturethereof.
 11. The method according to claim 10, wherein the secondsiloxane has a Shore Hardness of 00-30, 00-40, 00-50, or a mixturethereof.
 12. The method according to claim 9, wherein the first siloxaneis present in an amount of 2-20% by weight relative to the total weightof the combination.
 13. The method according to claim 9, wherein thefirst siloxane is present in an amount of 80-98% by weight relative tothe total weight of the combination.
 14. The method according to claim9, wherein the combination comprises a first siloxane having a ShoreHardness of 00-10 which is present in an amount from 25-35% by weight,and a second siloxane having a Shore Hardness of 00-30 which is presentin an amount from 65-75% by weight.
 15. The method according to claim 9,wherein the first siloxane has a Shore Hardness of 00-10, the secondsiloxane has a Shore Hardness of 00-30, the first siloxane comprises0-30% by weight of the combination, and the second siloxane comprises70-100% by weight of the combination.
 16. The method according to claim9, wherein the skin simulant is a vaginal skin simulant.